This proposal is designed to elucidate the role of calcium blockade in the protection of the kidney from postischemic renal failure (PIRF) after surgically induced ischemia, and the effects of ischemia prior to renal transplantation. Data from this laboratory indicate that treatment of the ischemic kidney with the calcium blocker verapamil during the reflow period after ischemia protects the ischemic kidney in both rats and dogs. In the conscious, chronically instrumented ewe, renal ischemia will be induced by occlusion of the renal arteries bilaterally for 1 1/2 hours. The effects of verapamil and nifedipine on PIRF will be examined by infusion of one of these calcium blockers into one renal artery and saline into the contralateral renal artery for 60 min. Renal blood flow will be measured using microspheres. Renal autoregulatory capacity will also be tested. Tubular function will be assessed by inulin clearance, osmotic and free water clearances, and fractional excretion of sodium and calcium. Glomerular and tubular morphology will be examined using light, scanning and transmission electon microscopy. All measurements will be performed during the pre-ischemic period and at 30 min., 24 hours, and 7 days postischemia. The effect of verapamil on posttransplant acute renal failure will be assessed in conscious ewes after autotransplantation of a kidney subjected to 30 min. of warm ischemia and 24 hours of cold storage in Collins C4 solution. Renal structure and function will be assessed as in other experiments in the conscious animals. Data obtained from these studies will add to present knowledge of PIRF and help define the role of therapeutic intervention in the management of acute renal ischemia and renal preservation for transplantation.